Ichthyosis, Erythrokeratolysis Hiemalis

The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1988, 1989, 1991, 1992, 1993, 1997, 2006

Synonyms of Ichthyosis, Erythrokeratolysis Hiemalis

Disorder of Cornification 19 (Erythrokeratolysis Hiemalis)

DOC 19

Erythrokeratolysis Hiemalis

Keratolytic Winter Erythema

Oudtshoorn Skin

Disorder Subdivisions

No subdivisions found.

General Discussion

Erythrokeratolysis hiemalis is an extremely rare form of ichthyosis that was first described in South Africa but has subsequently been identified in other countries. In such cases, a link to South Africa has been determined. The disorder is characterized by periodic attacks of red (erythematous) plaques that are distributed equally on both sides of the body. A layer of skin can be peeled from these plaques. Symptoms usually improve with age. The disorder tends to become worse with the cold weather.

Symptoms

Erythrokeratolysis hiemalis is characterized by periodic attacks of red skin plaques. A thick layer of skin can be peeled off these plaques from the center outward. As new skin forms, the plaques are pushed outward. Symptoms may start during infancy or adolescence, and the disorder usually improves with age. Only the palms of the hands and the soles of the feet are involved in most cases. However, the disorder may spread to the skin of the back or elsewhere on the body surface. Appearance of new plaques may be precipitated by fever or surgery.

Causes

Erythrokeratolysis hiemalis is a hereditary disorder transmitted as an autosomal dominant trait. The mutated gene has been tracked to gene map locus 8p23-p22.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 8p23-p22" refers to the region on the short arm of chromosome 8 between bands 23 and 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Erythrokeratolysis hiemalis primarily affects descendants of farmers from the Oudtshoorn district in South Africa. This disorder starts during infancy or adolescence and usually improves after age 30. It is thought to affect males and females equally. One estimate is that 37 babies are born with this disorder annually.

Related Disorders

Symptoms of the following disorders may be similar to those of erythrokeratolysis hiemalis. Comparisons can be useful for a differential diagnosis:

"Ichthyosis" or "disorders of cornification" are general terms describing a group of scaly skin disorders. They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin. The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of skin cells known as "corneocytes" or of the fat-rich matrix around these cells. The cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (For more information, choose "Ichthyosis" as your search term in the Rare Disease Database.)

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry and rough skin, with large, coarse scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet is abnormally thick. (For more information, choose "Ichthyosis Congenita" as your search term in the Rare Disease Database.)

X-linked ichthyosis is an inherited skin disorder affecting males. It is caused by a deficiency of the enzyme steroid sulfatase. This enzyme deficiency leads to biochemical alterations in steroid hormone metabolism. Cholesterol sulfate may accumulate in the blood and skin. (For more information, choose "X-Linked Ichthyosis" as your search term in the Rare Disease Database.)

Other forms of ichthyosis include Sjogren-Larsson syndrome, Netherton syndrome, ichthyosis hystrix, lamellar ichthyosis, Refsum syndrome, Darier disease, Conradi-Hunermann syndrome, Chanarin-Dorfman syndrome, and epidermolytic hyperkeratosis. (Choose the appropriate name as your search term for more information on that disorder in the Rare Disease Database.)

Standard Therapies

Diagnosis
In most instances, the appearance of the skin determines the diagnosis, but a family history and physical examination are often required to rule out other possible causes of scaly, dry skin. Some physicians may examine skin tissue under a light microscope or even under an electron microscope.

Treatment
Therapy is symptomatic and focuses on diminishing the build-up of skin (hyperkeratosis). Systemic therapy with oral retinoids is very effective, but has to be carefully monitored because of side effects. Moreover, the treatment is effective for only as long as one takes the medication. After treatment is stopped, the skin build-ups reappear within a short period of time. Topical skin care may include emollients and keratolytics such as: urea, lactic acid, glycolic acid, propylene glycol, salicylic acid, and topical retinoids preparations. Avoiding mechanical irritation of the skin can be beneficial.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Drugs derived from vitamin A (retinoids) such as tretinoin, motretinide, and etretinate may be effective against symptoms of erythrokeratolysis hiemalis, but can cause toxic effects on the bones in some cases. A synthetic derivative of vitamin A, isotretinoin, when taken by pregnant women, can cause severe birth defects to the fetus. These vitamin A compounds have not yet been approved by the Food and Drug Administration (FDA) for treatment of ichthyosis.

The National Institute of Arthritis, Musculoskeletal and Skin Diseases is looking for patients with various kinds of ichthyosis willing to participate in research aimed at mapping the genes responsible for their disorder. Interested persons may contact:

The orphan product monolaurin (Glylorin), a topical cream, is being tested for treatment of Ichthyosis. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of ichthyosis. For more information, contact:

Ichthyosis, Erythrokeratolysis Hiemalis Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)